Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences.
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ABSTRACT:
SUBMITTER: Carbonaro TM
PROVIDER: S-EPMC5551678 | biostudies-other | 2016 Dec
REPOSITORIES: biostudies-other
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Project description:SLC30A8 encodes the zinc transporter ZnT8. SLC30A8 haploinsufficiency protects against type 2 diabetes (T2D), suggesting that ZnT8 inhibitors may prevent T2D. We show here that, while adult chow fed Slc30a8 haploinsufficient and knockout (KO) mice have normal glucose tolerance, they are protected against diet-induced obesity (DIO), resulting in improved glucose tolerance. We hypothesize that this protection against DIO may represent one mechanism whereby SLC30A8 haploinsufficiency protects against T2D in humans and that, while SLC30A8 is predominantly expressed in pancreatic islet beta cells, this may involve a role for ZnT8 in extra-pancreatic tissues. Consistent with this latter concept we show in humans, using electronic health record-derived phenotype analyses, that the 'C' allele of the non-synonymous rs13266634 SNP, which confers a gain of ZnT8 function, is associated not only with increased T2D risk and blood glucose, but also with increased risk for hemolytic anemia and decreased mean corpuscular hemoglobin (MCH). In Slc30a8 KO mice, MCH was unchanged but reticulocytes, platelets and lymphocytes were elevated. Both young and adult Slc30a8 KO mice exhibit a delayed rise in insulin after glucose injection, but only the former exhibit increased basal insulin clearance and impaired glucose tolerance. Young Slc30a8 KO mice also exhibit elevated pancreatic G6pc2 gene expression, potentially mediated by decreased islet zinc levels. These data indicate that the absence of ZnT8 results in a transient impairment in some aspects of metabolism during development. These observations in humans and mice suggest the potential for negative effects associated with T2D prevention using ZnT8 inhibitors.
| S-EPMC7351606 | biostudies-literature
Project description:BackgroundCurrently, there are few empirical studies that demonstrate the effects of music on specific emotions, especially in the educational context. For this reason, this study was carried out to examine the impact of music to identify affective changes after exposure to three musical stimuli.MethodsThe participants were 71 university students engaged in a music education course and none of them were musicians. Changes in the affective state of non-musical student teachers were studied after listening to three pieces of music. An inter-subject repeated measures ANOVA test was carried out using the Positive and Negative Affect Schedule (PANAS) to measure their affective state.ResultsThe results revealed that: (i) the three musical experiences were beneficial in increasing positive affects and reducing negative affects, with significant differences between the interaction of Music Experiences × Moment (pre-post); (ii) listening to Mahler's sad fifth symphony reduced more negative affects than the other experimental conditions; (iii) performing the blues had the highest positive effects.ConclusionsThese findings provide applied keys aspects for music education and research, as they show empirical evidence on how music can modify specific affects of personal experience.
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Project description:Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes. The transcriptomic study comprises 16 samples from Lymph node metastasis from infiltrating ductal breast carcinoma, 18 samples from Primary node-positive infiltrating ductal,7 samples from Primary node-negative infiltrating ductal and 3 samples from Unaffected lymph node were included. Their RNA was isolated and prepared for hybridization to human Affymetrix GeneChip arrays.
2013-03-05 | E-GEOD-44408 | biostudies-arrayexpress
Project description: Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and –positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes.
2013-03-05 | GSE44408 | GEO
Project description:This study tested a model linking work experiences to employee alcohol use. The model extended past research in 3 ways. First, it incorporated both negative and positive work experiences. Second, it incorporated a previously unexplored cognitive intervening process involving negative and positive work rumination. Third, it incorporated several important dimensions of alcohol use (heavy use, workday use, and after-work use). Data were collected from a national probability sample of 2,831 U.S. workers. Structural equation modeling revealed that the conceptual model provided an excellent fit to the data. Negative work experiences were positively related to negative work rumination, which was positively related to heavy alcohol use, workday alcohol use, and after work alcohol use. Positive work experiences were positively related to positive work rumination, which was negatively related to heavy alcohol use and after work alcohol use, but was unrelated to workday alcohol use. The study also provided initial support for the psychometric properties and construct validity of the newly developed Negative and Positive Work Rumination Scale (NAPWRS).
| S-EPMC4372465 | biostudies-literature
Project description:Group A Streptococcus (GAS) skin infections are caused by a diverse array of strain types and are highly prevalent in disadvantaged populations. The role of strain-specific immunity in preventing GAS infections is poorly understood, representing a critical knowledge gap in vaccine development. A recent GAS murine challenge study showed evidence that sterilising strain-specific and enduring immunity required two skin infections by the same GAS strain within three weeks. This mechanism of developing enduring immunity may be a significant impediment to the accumulation of immunity in populations. We used an agent-based mathematical model of GAS transmission to investigate the epidemiological consequences of enduring strain-specific immunity developing only after two infections with the same strain within a specified interval. Accounting for uncertainty when correlating murine timeframes to humans, we varied this maximum inter-infection interval from 3 to 420 weeks to assess its impact on prevalence and strain diversity, and considered additional scenarios where no maximum inter-infection interval was specified. Model outputs were compared with longitudinal GAS surveillance observations from northern Australia, a region with endemic infection. We also assessed the likely impact of a targeted strain-specific multivalent vaccine in this context. Our model produced patterns of transmission consistent with observations when the maximum inter-infection interval for developing enduring immunity was 19 weeks. Our vaccine analysis suggests that the leading multivalent GAS vaccine may have limited impact on the prevalence of GAS in populations in northern Australia if strain-specific immunity requires repeated episodes of infection. Our results suggest that observed GAS epidemiology from disease endemic settings is consistent with enduring strain-specific immunity being dependent on repeated infections with the same strain, and provide additional motivation for relevant human studies to confirm the human immune response to GAS skin infection.
| S-EPMC7299408 | biostudies-literature
Project description:BackgroundA better understanding of the long-term health effects of combat injury is important for the management of veterans' health in the Department of Defense (DoD) and Veterans Affairs (VA) health care systems and may have implications for primary care management of civilian trauma patients.ObjectiveTo determine the impact of traumatic injury on the subsequent development of hypertension (HTN), diabetes mellitus (DM), and coronary artery disease (CAD) after adjustment for sociodemographic, health behavior, and mental health factors.DesignRetrospective cohort study of current and former US military personnel with data obtained from both the DoD and VA health care systems.ParticipantsCombat injured (n = 8727) service members between 1 February 2002 and 14 June 2016 randomly selected from the DoD Trauma Registry matched 1:1 based on year of birth, sex, and branch of service to subjects that deployed to a combat zone but were not injured.Main measuresTraumatic injury, stratified by severity, compared with no documented injury. Diagnoses of HTN, DM, and CAD defined by International Classification of Diseases 9th or 10th Revision Clinical Modification codes.Key resultsAfter adjustment, severe traumatic injury was significantly associated with HTN (HR 2.78, 95% CI 2.18-3.55), DM (HR 4.45, 95% CI 2.15-9.18), and CAD (HR 4.87, 95% CI 2.11-11.25), compared with no injury. Less severe injury was associated with HTN (HR 1.14, 95% CI 1.05-1.24) and CAD (HR 1.62, 95% CI 1.11-2.37).ConclusionsSevere traumatic injury is associated with the subsequent development of HTN, DM, and CAD. These findings have profound implications for the primary care of injured service members in both the DoD/VA health systems and may be applicable to civilian trauma patients as well. Further exploration of pathophysiologic, health behavior, and mental health changes after trauma is warranted to guide future intervention strategies.
| S-EPMC7947104 | biostudies-literature
Project description: Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and –positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes. The transcriptomic study comprises 16 samples from Lymph node metastasis from infiltrating ductal breast carcinoma, 18 samples from Primary node-positive infiltrating ductal,7 samples from Primary node-negative infiltrating ductal and 3 samples from Unaffected lymph node were included. Their RNA was isolated and prepared for hybridization to human Affymetrix GeneChip arrays.
| S-ECPF-GEOD-44408 | biostudies-other
Project description:Luminal advanced breast cancer (ABC) patients eventually progress on endocrine therapy. REVERT aimed to explore whether eribulin could restore endocrine sensitivity in a randomized, non-comparative phase II trial. Aromatase inhibitor (AI)-resistant patients with luminal ABC were randomized 1:1 to receive eribulin +/- AI. Patients were stratified by prior cyclin-dependent kinases 4/6 inhibitor (CDK4/6i) treatment. The primary endpoint was an investigator-assessed overall response rate (ORR) according to RECIST version 1.1 in the eribulin + AI arm. An interim analysis was planned with 11 evaluable patients according to a two-stage Simon design. Twenty-two patients were enrolled (15 eribulin + AI arm; 7 eribulin arm). The trial was terminated early in March 2021, with eight (36.4%) patients still on treatment. ORR was 26.7% in the eribulin + AI arm (95% CI, 7.8-55.1%; p = 0.0541). In the eribulin arm, two (28.6%) patients had an objective response (95% CI, 3.7-71.0%). The difference between the study arms was not significant (p = 0.918). The addition of AI to eribulin also failed to show improvement in other efficacy endpoints. A significant interaction between the treatment arm and previous CDK4/6i treatment was observed for ORR (p = 0.018) and progression-free survival (p = 0.084). Overall, the toxicity profile was consistent with the known safety profile of eribulin. No treatment-related deaths were reported. Eribulin + AI does not seem to improve outcomes compared with eribulin monotherapy in patients with AI-resistant luminal ABC. This chemo-endocrine approach deserves further investigation after progression to CDK4/6i-based therapy.
| S-EPMC9737152 | biostudies-literature
Project description:Persons diagnosed with cancer during adolescence have reported negative and positive cancer-related consequences two years after diagnosis. The overall aim was to longitudinally describe negative and positive cancer-related consequences reported by the same persons three and four years after diagnosis. A secondary aim was to explore whether reports of using vs. not using certain coping strategies shortly after diagnosis are related to reporting or not reporting certain consequences four years after diagnosis. Thirty-two participants answered questions about coping strategies shortly after diagnosis and negative and positive consequences three and four years after diagnosis. Answers about consequences were analysed with content analysis, potential relations between coping strategies and consequences were analysed by Fisher's exact test. The great majority reported negative and positive consequences three and four years after diagnosis and the findings indicate stability over time with regard to perceived consequences during the extended phase of survival. Findings reveal a potential relation between seeking information shortly after diagnosis and reporting a more positive view of life four years after diagnosis and not using fighting spirit shortly after diagnosis and not reporting good self-esteem and good relations four years after diagnosis. It is concluded that concomitant negative and positive cancer-related consequences appear stable over time in the extended phase of survival and that dialectical forces of negative and positive as well as distress and growth often go hand-in-hand after a trauma such as cancer during adolescence.
| S-EPMC3237575 | biostudies-literature